Alkylene bis benzoxazine compounds



2,825,728 Fatented Mar. 4, 1958 from 1 to 4 carbon atoms, inclusive, or a cyclohexylidene radical, and A represents a radical having the structure 2,825,728 OH ALKYLENE BIS BENZOXAZINE COMPOUNDS 5 0 0 1 Raymond H. Rigterink, Midland, Mich., assignor to The I I I )ow Chemical Company, Midland, Mich., a corpora- Halogen V D of Delaware in which D is hydrogen, halogen or methyl.

No Drawing. Application December 12, 1956 In the first step of the reaction, a primary amine such Serial No. 627,747 as aniline, haloaniline, benzylarnine, halobenzylamine cy- 6 Claims (Cl. 26a 244) clohexylamine, or an alkylamine is added to formaldehyde or formaldehyde yielding substance in a solvent inert under the conditions of reaction such as methanol, ethanol or dioxane. The reaction takes place smoothly at the temperature range of from 0 to 50 C. with the formation of the desired intermediate formaldehyde condensa- (Z) =R tion product of the amine. The reaction is somewhat In this and succeeding formulae, R represents an alkylexothermic and coolmg may be required 9 mamtam idene radical containing from 1 to 4 carbon atoms, incluperaiure control Good resulis are obtamefl i sive, or a cyclohexylidene radical, and Z represents a ploymg one molgcplar Propomon of the amme Wnh two radical having the structure molecular proportions of formaldehyde. When a formaldehyde yielding substance is used as a reactant, this substance is employed in an amount equivalent to the desired The present invention is concerned with the benzoxazine compounds having the formula 0 amount of formaldehyde.

l In the second step of the reaction, the alkylidene bis- \C/ halogen phenol or cyclohexylidenebisphenol is added to the reaction mixture prepared as described above. In such operaor tions, one-half molecular proportion of the bisphenol compound is employed for each molecular proportion of X the primary amine used in the preparation of the intermedi- 0 ate formaldehyde condensation product of the amine.

Ki o The reaction takes place smoothly at the temperature range of from 30 to 100 C. The desired product may precipitate from the reaction mixture during the heating H2 period or upon cooling the mixture after completion of i which Y is cyclohexyl benzyl, phenyl, halobenzyl, ha1o the reaction. The product, if a solid, is removed from the phenyl or an alkyl radical containing from 1 to 12 carcoded mlxture by Punfied by ccfnvenilonal hon atoms, inclusive and X is hydrogen, halogen or methods such as recrystallization. The product, if an methyl. The term alkylidene as used in the present be isolated from Eamon by ifi ti and claims refers to a divalent aliphatic adding thereto toluene, (2) agitating the resulting hetero radical derived from an aliphatic hydrocarbon by the regeneous mime, (3) mchamcany erg the aqua moval of two hydrogen atoms from one of the carbon 0115 and toluene fracuons, (4) g s the toluene at0ms fraction to remove low boiling constituents and recover The new compounds are crystalline solids or oily liquids the deslred P P as a reslfluesomewhat soluble in many organic solvents such as The followmg examples lllllstrate 111E mventlofl. but toluene, ethyl acetate and petroleum ether and of a very are not t0 be ccnstlued as limiting:

Example 1.6,6-isopropylidenebis(3-cyclohexyl-3,4- dihydro-ZH-i,3-benzoxazine) low solubility in water. The compounds are particularly Sixty grams of paraformaldehyde (equivalent to two useful as parasiticides and are adapted to be employed as moles of HCHO), 1.0 gram of potassium hydroxide and active toxic constituents of compositions for the control 150 milliliters of methanol were mixed together and the of many pests such as flies. resulting mixture heated to the boiling temperature,

The new compounds may be prepared by causing a C., to obtain a clear solution. The reaction vessel and primary amine having the formula YNH to react wi h 65 contents were then cooled to room temperature and 1.0 a formaldehyde or a formaldehyde yielding substance to mole (99 grams) of cyclohexylamine added portionwise form an intermediate formaldehyde condensation product t r T a ii n as arri d Out with Stirring and of the amine. The latter is then caused to react with a external cooling and at a p rature of from 25 to 30 bisphenol compound having the formula C. Upon completion of the addition, 0.5 mole (114 A) grams) of 4,4-isopropylidenebisphenol was added to the mixture and the resulting mixture heated at the boiling wherein B represents an alkylidene radical containing temperature, 82-86" C., and under reflux for one hour.

t V A a t 'The reaction vessel and contents were thereafter cooled tionmixture. and the resulting mixture heatedrwith to room temperature and the reaction mixture diluted 7 ring at the boiling temperature, 8286 C., and under i with f fll) milliliters oi toluene and 250 milliliters of water. reflux for one hour. The reaction mixture was then Upon agitation, the diluted mixture" separated into an cooled and diluted with 250 milliliters of toluene. The

aqueous layer and an organic layer.AThe.latter wasrse'pdiluted mixture was thereafter processed as described in arated by decantation and fractionally distilled under re Example 1 to obtain a 6;6fcyfclbhexylidenebis(S-cycloduced pressure to remove low boiling constituents and obhexyl-3,4-dihydro 2H;1 3=benzoxazine), product, as. an tain a 6,6 -isopropylidenebis(3 -cyclohexyl-3 ,4-dihydrooily residue. 6;6 cyelbhexylidenebis(3'-oyclohexyl=?;4-'

2Hl,3-benzoxazine) product as a viscouslliquid. 6,6'- dlhydro-ZH-1;3-benzoxazine) has amolecularweight of 7 isopropylidenebis(3 {cyclohexyl- 3,4 -di hydr o 2H -1,3- 10 514.7. r a M befnzoxazme) ha t q a l i fi I Example 4.6,6'-is0propylidenebis [3,4 difiyiir'0-3'-' i Example 2.,8,8'-methyler'zebis(6-chl0r -3,4-dihydr0-3- r V (paraclzlorophenyl)-2HZ,3-benzoxazine] a phenyl-2H L3-benz0xazine) a i /0 on; 1 7 I GI-O-N -o1 \0/ V i .7; Hg CH:

portionwise over a minute period to a mixture of 60 grams of paraformaldehyde (-2.0 mole equivalents of permeatin (1.6 mole; 1127- tgaaey was ttng Sixty gjrfinisj r pnard nnnee'iiyee zon l; e ql liv a 1HCHO).and one gram 0r potassium hydroxide dispersed tents of HQHQ)"onegian1,0i potassium hydroxide and in 80 milliliters of methanol. The addition was carried? 8 0 fmillil r's'j of' methanol ere mixed togethe'ry and outwith stirring and cooling and at a' temperatureyof' warmed fo 'the boiling ternperature; 65" C,,' toolitain a from 25 to 35 C. Upon completion of the addition; clear s 'olutionl 'Tlfe r'eactionvesseland 'eontents we're 0.5 mole (114 grams) of 4,4'-isopropylidenebisphenol then" ooled tor'oom temperature g uge moe' 93; was added to the reaction mixture and the resulting gr ms) of aniline added portionwis'e to the reaction mix mixture heated with stirring at the boiling temperature,

' titre over a 1Sj minute'period, I hetaddition wasjcarriee 8286 C., and under refiux forne-half hour. The

outwith stirring'fand cooling; and at a temperatureof reaction mixture was thencooled and diluted with-250 fro'fit zsft t sofcg ljpo completion ofthfe atiifirion; milliliters of toluene. The diluted mixture was there- 0L5 mole 1'2 3; grams) of Z,2'-methylenebis(4-chl6ro after processed as described in Example 2 to obtain a.

phenol) added flto the reac'tion rnixture and the reg v 6,6 isopropylidenebis [3,4 dihydro 3 (para chlorou1tinm1xturelieated at the boiling tem Era'ture SZ phenyl)-2H-1,3-benzoxaiine] product as a crystalline to 86 Qi-andunderrefiux'tor one hour, The reaction solid. This product was recrystallized from ethyl acefhe'ncooled; in anic'e' bath and dilutedwith tate and found to melt at 150 153 C.

r d 6 H20 ?Hl V ritc-nio mo-nio-n "N-cHFonFont -om V \g' 7 \C/' 250 milliliters'of toluenei The diluted mixture sepa Normal-butylaminetLO mole; 73 grams) was added ratedin p q s d a c aye s- T o ga c are: ref-5 5%; oft'S minutes to sixty" grains was separated and tifie y.i sfi fifi a we at p aform aeti tie (2-6 mole' eqirivalentsof Honor pressure of 10 millimeters to afinal temperature of 100 ag s y fia a p z C. to remove low boiling constituents and obtain an 8,8- methylenebis clil orp 3 4t-;dihydro 3:phenyl-2H+1,3 benzoxazine) product ca erysfalline residue. Thi

with stirring and cooling and at a temperature of from product was recrystallized from ethyi'aeetate and found to 35 UPOIl completion the addififlll,

' to melt'at 155-157 C.

mole (100 grams) of 2,2'-methylenebis( l-chlorophenol') 'c c'toiiexynmmeup mete; gas-giant's) wajsidiiaiper; wa'saddedfpg iqnw e r m ms' e d' era j -b re ult n ix u e l nden. r flux J gram of. potassium hydroxide dispersledinffiOQmilliliters mixture was'tliereafler processed as, desciilid 5 153;-

of methanol. The ad orrwascar ed jout with stlrrmg j ample 2 to obtainfan'8i8' nithylenebis( 3 n6rmal b y! and icoolin g andtataternpera ennan 251ml 6-chloro-3,4-dihydro 2H1,3 henzoxazine) product as a i jfl nl ile 1 4 i P X c n s l d. Ih lepr ducti a u ccn t l q {r99 or'4;4' c e1eheiy1idefiebisphenor'tvastiaded te 'thereae etliyl fitateaiiil fdundiomelf'at7830 C;

milliliters of methanol. The addition was carried out "i s if l ew P ma te iid ated at the boiling temperature irringfor-onehourz' The reaction mamas-- .5 6 Example 6.--8,8'-merhylenebis(3-benzyl-6-chloro-3,4- dihydro-2H -1 ,3-benzoxazine C H: Benzylamine (1.0 mole; 106 grams) was added poroxazine) product as a viscous oily residue 6,6-(2-butyltionwise over a minute period to sixty grams of paraidene)bis(3,4 dihydro 3 cyclohexyl-Zl-I 1,3 benzformaldehyde (2.0 mole equivalents of HCHO) and one oxazine) has a molecular weight of 488.7. gram of potassium hydroxide dispersed in 80 milliliters In a similar manner other benzoxazine compounds of methanol. The addition was carried out with stir- 15 may be prepared as follows: ring and cooling and at a temperature of from 25 to 8,8 methylenebis(6 chloro 3,4-dihydro-3-methy1- 35 C. Upon completion of the addition, 0.5 mole (100 2H-1,3-benzoxazine) by reacting methylamine, formalgrams) of 2,2-methylenebis(4-chlorophenol) was added dehyde and 2,2'-methylenebis(4-chlorophenol). ThlS portionwise to the reaction mixture and the resulting product is a white crystalline solid melting at 152- mixture heated with stirring at the boiling temperature 154.5 C.

and under reflux for one hour. The reaction mixture was 8,8 methylenebisl6 chloro 3,4 dihydro 3 (pthereafter processed as described in Example 2 to obtain chlorophenyl)-2H-l,3-benzoxazine] by reacting p-chloroan 8,8-methylenebis(3-benzyl-6-chloro-3,4-dihydro-2H- aniline formaldehyde and 2,2'-methylenebis(4-chloro- 1,3-benzoxazine) product as a crystalline solid. This phenol). This product is a light purple crystalline solid product was recrystallized from ethyl acetate and found melting at 187-l90 C. to melt at 119.5 -121.5 C. 6,6 isopropy1idene(3 cyclohexyl 3,4 dihydro 8- Example 7.-6,6'-is0pr0pylidenebis(8-chl0r0-3-cycl0- hexyl-3,4-dihydro-2H-1,3-benzoxazine) H, H; H: H: Cyclohexylamine (1.0 mole; 93 grams) was added pormethyl-2H-1,3-benzoxazine) by reacting cyclohexyltionwise over a 15 minute period to 60 grams of paraamine, formaldehyde and 4,4-isopropylidenebis(oformaldehyde (2 more equivalents of l-ICHO) and one cresol). 6,6 isopropylidenebis(3 cyclohexyl -3,4- gram of potassium hydroxide dispersed in 80 milliliters 4 dihydro-S-methyl-ZH-1,3-benzoxazine) has a molecular of methanol. The addition was carried out with stirring weight of 474.

and cooling and at a temperature of from 25 to C. 8,8 methylenebis(6 bromo 3,4 dihydro 3- Upon completion of the addition, 0.5 mole (148.5 grams) normal-dodecyl-ZH-l,3-benzoxazine) by reacting normalof 4,4isopropy1idenebis (2-chlorophenol) was added dodecylamine, formaldehyde and 2,2-methylenebis(4- portionwise to the reaction mixture and the resulting mixbromophenol).

ture heated with stirring at the boiling temperature and 6,6 (1 propylidene)bis(3 benzyl 3,4 dihydrounder reflux for one hour. The reaction mixture was 2F-l,3-benzoxazine) by reacting benzylamine, formalthereafter processed as described in Example 1 to obdehyde and 4,4'-(l-propylidene)bisphenol.

tain a 6,6'-methylenebis(8-chloro-3-cyclohexyl-3,4-di- 6,6 (1 butylidene)bis(3 normal butyl 3,4-

hydro-ZH-1,3-benzoxazine) product as a viscous oily dihydro-2H-1,3-benzoxazine) by reacting normal-butylresidue. 6,6-methylenebis(8-chloro-3-cyclohexyl-3,4-diamine, formaldehyde and 4,4'-(1-butylidene)bisphenol. hydro-2H-l,3-benzoxazine) has a molecular weight of 6,6 isopropylidenebis[3 (p bromobenzy1)3,4-di- 534.6. hydro-8-methyl 2H 1,3 benzoxazine] by reacting p- Example 8.6,6- (Z-butylidene)bis(3-cyclohexyl-3,4-dihydro-2H-L3-benzoxazine) a Hz H: v 0-c Hit on, on: o-o c C o--o H H (3-0 H, H, H, H; CH3 Cyclohexylamine (1.0 mole; 93 grams) was added bromobenzylamine, formaldehyde and 4,4'-isopropylportionwise over a 15 minute period to grams of paraidenebis(o-cresol).

formaldehyde (2 mole equivalents of HCHO) and one 8,8 (1 propylidene)bis(6 bromo 3 cyclohexylgram of potassium hydroxide dispersed in 80 milliliters 3,4-dihydro-2H-1,3-benzoxazine) by reacting cyclohexylof methanol. The addition was carried out with stirring amine, formaldehyde and 2,2'-(1-propylidene)bis(4- and cooling and at a temperature of from 25 to 35 C. bromophenol).

Upon completion of the addition, 0.5 mole (120 grams) 6,6 methylenebis[3,4 dihydro 3 (2,4,5 triof 4,4-(2-butylidene) bisphenol was added portionwise chlorophenyl)-2I-I-l,3-benzoxazinelby reacting 2,4,5- to the reaction mixture and the resulting mixture heated trichlorophenylamine, formaldehyde and 4,4'-methy1enewith stirring at the boiling temperature and under reflux bisphenol.

for one hour. The reaction mixture was thereafter proc- The compounds of the present invention have been essed as described in Example 1 to obtain a 6,6-(2-butyltested and found to be efiective as parasiticides. In such idene)bis(3,4 dihydro 3 cyclohexyl 2H 1,3 benzuse the compounds may be employed in admixture with a finely'divided solid. Also, such mixtures may be dis- Q persed in water with the aid of a wetting agent. In

other procedures, the compounds may be employed in admixture with a liquid carrier such as water, a suitable solvent or an aqueous emulsion. In representative operations, substantially complete controls of the common house fly (Musca domestica) have been obtained with" aqueous spray Compositions containing 0.24 percent by weight of 6,6'-isopropylidenebis (3-norma1-buty1-6-chloro 13,4-dihydro-2H-1, 3-benzoxazine) wherein R represents a member of the group consisting ili elky m ad als cnt ini m 1 51v carbon atoms, inclusive, and a cyclohegrylidene radical, and Z represents one of the radicals having the structure v .t 1 L Fe ini t agent asses es in which Yis selected 'fr'om'the groupconsisiingoi cycle hexyl, benzyl; phenyl, halobeniyl, halophenyl and the alkyl radicals containing from 1 -to 12 carbon atoms in- V ql hszyl; 13,4; disc hydrO- ZI- I-Livf-benz'bxazine), V V

4- 8,8, n hy neb fl hlo q 13A hy t'o 3. PhEnYL-ZH- fihw naiinci- V 5. 8,8 methylenebis(3 normal -,buty l 67 3 ,4-2H-l;3-bengoxazine). c a V V V 6.[8 ,8' methylenebisfii chloro -3 ;4 dihydro 3T- meth lli l inzoxaz ne) i a No references cited.

'-' chloro:

U. S. DEPARTMENT OF COMMERCE PATENT OFFICE C ERTIFICATE OF C ORREC TION Raymond Rigterink March 4, 1958 ror appears .in the printed specification that the said Letters Patent Noa 2 825 '728 It is hereby certified that er of the above numbered patent requiring correction and I Patent should read as corrected below.

Column 8 line 21 for "3,4=2H=-l,3=benzoxazine)" read 3,4-dihydro- 2H=l 3=benzoxazine) a Signed and sealed this 24th day of June 1958x (SEAL) Attest:

KARL H AXLINE Attesting Officer ROBERT C WATSON Comnissioner of Patents 

1. A BENZOXAZINE A MEMBER OF THE GROUP CONSISTING 